BRCA1 Protein Expression Predicts Survival in Glioblastoma Patients from an NRG Oncology RTOG Cohort.

PURPOSE: Glioblastoma, the most common malignant brain tumor, was associated with a median survival of <1 year in the pre-temozolomide (TMZ) era. Despite advances in molecular and genetic profiling studies identifying several predictive biomarkers, none has been translated into routine clinical use. Our aim was to investigate the prognostic significance of a panel of diverse cellular molecular markers of tumor formation and growth in an annotated glioblastoma tissue microarray (TMA). METHODS AND MATERIALS: A TMA composed of archived glioblastoma tumors from patients treated with surgery, radiation, and non-TMZ chemother-apy, was provided by RTOG. RAD51, BRCA-1, phosphatase and tensin homolog tumor suppressor gene (PTEN), and miRNA-210 expression levels were assessed using quantitative in situ hybridization and automated quantitative protein analysis. The objectives of this analysis were to determine the association of each biomarker with overall survival (OS), using the Cox proportional hazard model. Event-time distributions were estimated using the Kaplan-Meier method and compared by the log-rank test. RESULTS: A cohort of 66 patients was included in this study. Among the 4 biomarkers assessed, only BRCA1 expression had a statistically significant correlation with survival. From univariate analysis, patients with low BRCA1 protein expression showed a favorable outcome for OS (p = 0.04; hazard ratio = 0.56) in comparison with high expressors, with a median survival time of 18.9 versus 4.8 months. CONCLUSIONS: BRCA1 protein expression was an important survival predictor in our cohort of glioblastoma patients. This result may imply that low BRCA1 in the tumor and the consequent low level of DNA repair cause vulnerability of the cancer cells to treatment.

Treatment modalities in sinonasal mucosal melanoma: A national cancer database analysis.

OBJECTIVES/HYPOTHESIS: The purpose of this study was to investigate the association of demographic factors, tumor stage, and treatment modalities for overall survival in patients with sinonasal mucosal melanoma (SNMM). STUDY DESIGN: Retrospective database review. METHODS: The National Cancer Database was queried for patients of all ages with SNMM between 2004 and 2015. Univariate Kaplan-Meier and multivariate Cox regression analyses were performed to evaluate the association of suspected prognostic factors with overall survival. RESULTS: A total of 1,874 patients with SNMM were included in the analysis. The 5-year overall survival was 24%. Prognostic factors associated with decreased survival include advanced age (hazard ratio [HR]: 1.02, 95% confidence interval [CI]: 1.01-1.03), T4 disease (HR: 1.44, 95% CI: 1.09-1.89), and presence of distant metastases (HR: 3.22. 95% CI: 2.06-5.04). Improved survival was associated with surgical resection only when margins were negative (HR: 0.44; 95% CI: 0.30-0.65). In patients with metastatic disease, administration of immunotherapy (HR: 0.14; 95% CI: 0.04-0.49) was associated with improved survival. Surgical approach, radiotherapy, and chemotherapy were nonsignificant predictors of survival. CONCLUSIONS: This investigation is the largest to date to analyze the association of treatment modalities with overall survival in SNMM. Surgery remains the mainstay of treatment in patients with SNMM. However, administration of immunotherapy may confer survival benefit to patients with metastatic disease. LEVEL OF EVIDENCE: NA Laryngoscope, 130:275-282, 2020.

Proton vs. Photon Radiation Therapy for Primary Gliomas: An Analysis of the National Cancer Data Base.

Background: To investigate the impact of proton radiotherapy (PBT) on overall survival (OS) and evaluate PBT usage trends for patients with gliomas in the National Cancer Data Base (NCDB). Methods: Patients with a diagnosis of World Health Organization (WHO) Grade I-IV glioma treated with definitive radiation therapy (RT) between the years of 2004-13 were identified. Patients were stratified based on WHO Grade and photon radiotherapy (XRT) vs. PBT. Univariate (UVA) and multivariable analysis (MVA) with OS were performed by Cox proportional hazards model and log-rank tests. Propensity score (PS) weighting was utilized to account for differences in patient characteristics and to minimize selection bias. Results: There were a total of 49,405 patients treated with XRT and 170 patients treated with PBT. Median follow-up time was 62.1 months. On MVA, the following factors were associated with receipt of PBT (all p < 0.05): WHO Grade I-II gliomas, treatment at an academic/research program, west geographic facility location, and surgical resection. After PS weighting, all patients treated with PBT were found to have superior median and 5 year survival than patients treated with XRT: 45.9 vs. 29.7 months (p = 0.009) and 46.1 vs. 35.5% (p = 0.0160), respectively. Conclusions: PBT is associated with improved OS compared to XRT for patients with gliomas. This finding warrants verification in the randomized trial setting in order to account for potential patient imbalances not adequately captured by the NCDB, such as tumor molecular characteristics and patient performance status. Importance of the Study: This is the first study that compares the outcomes of patients treated with photon based radiotherapy vs. proton based radiotherapy for patients with gliomas. In this retrospective analysis, the results demonstrate that proton therapy is associated with improved outcomes which support ongoing prospective, randomized clinical trials comparing the two modalities in patients with gliomas.

Locoregionally advanced oral cavity cancer: A propensity-score matched analysis on overall survival with emphasis on the impact of adjuvant radiotherapy.

BACKGROUND: The purpose of this study was to determine the impact of adjuvant radiotherapy (RT) in locoregionally advanced oral cavity cancer. METHODS: Data were extracted from the National Cancer Data Base, of which overall survival (OS) is the only outcome variable available. The chi-square test and Cox regression models were used. RESULTS: A total of 6654 patients were identified. The utilization of adjuvant RT has increased over time. A propensity matched cohort included 3946 patients, exactly one-half of whom received adjuvant RT. Independent predictors associated with receipt of adjuvant RT included age, Charlson/Deyo comorbidity score, extracapsular extension, surgical margins, and T and N classifications. On multivariable analysis, adjuvant RT remained an independent prognosticator for OS. CONCLUSION: Receipt of adjuvant RT is a prognostic factor associated with improved OS, its utilization has increased over time, and it should be considered for clinically suitable patients who have undergone resection for the disease.

Gliosarcoma in septuagenarians and octogenarians: What is the impact of adjuvant chemoradiation?

The objective of our study is to determine the impact of adjuvant chemoradiation on overall survival (OS) for gliosarcoma in septuagenarians and octogenarians. Data were extracted from the National Cancer Data Base (NCDB). Chi-square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 23.0 (Armonk, NY: IBM Corp.) for data analyses. 210 patients with gliosarcoma who underwent resection were identified. 168 (80.0%) patients received adjuvant chemoradiation, and 42 (20.0%) received adjuvant RT alone. Patients were more likely to receive adjuvant chemoradiation if they were male vs. female (85.3% vs. 71.6%, p=0.016). There was no significant difference in receipt of adjuvant therapy by year of diagnosis, age at diagnosis, race, Charlson/Deyo Score, treatment facility type, tumor size, or extent of surgery. Those who received adjuvant chemoradiation had significantly better one-year OS than those who received adjuvant radiation alone (35.3% vs. 16.2%, p<0.001). On subset analysis, this significant one-year OS benefit was observed in septuagenarians, those with Charlson/Deyo Score of 0, and in those with tumor size ≤5cm. On multivariate analysis, receipt of adjuvant chemoradiation and greater extent of resection were independent prognostic factors for improved OS. Our data suggests that adjuvant chemoradiation is an independent prognostic factor for improved OS in elderly patients with gliosarcoma, and the results of our study can serve as estimated benchmarks for outcome in this growing and important patient population. Its benefit, however, may be limited to septuagenarians and those with lower comorbidity burden.

Distinct histopathologic features of radiation-induced chronic sinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is a commonly observed sequela after radiation therapy to the paranasal sinuses. The histopathologic features of radiation-induced CRS have yet to be determined and may have major implications in disease management. METHODS: A structured histopathology report was utilized to analyze sinus tissue removed during functional endoscopic sinus surgery (FESS). Histopathology variables, Lund-Mackay score (LMS), and 22-item Sino-Nasal Outcome Test (SNOT-22) scores were compared among patients with radiation-induced CRS (CRSr), CRS without nasal polyps (CRSsNP), and CRS with nasal polyps (CRSwNP). RESULTS: Fifteen CRSr, 43 CRSsNP, and 56 CRSwNP patients who underwent FESS were analyzed. Compared with CRSsNP, CRSr cases had increased squamous metaplasia (40.0% vs 9.3%, p < 0.013) and subepithelial edema (53.3% vs. 2.3%, p < 0.001). Compared with CRSwNP, CRSr cases had fewer eosinophils per high-power field (20.0% vs 50.0%, p < 0.034), less basement membrane thickening (33.3% vs 76.8%, p < 0.002), and fewer eosinophil aggregates (0.0% vs 30.4%, p < 0.009). CRSr had significantly greater mean LMS (13.47 ± 5.13 vs 7.07 ± 4.79, p < 0.001) compared with CRSsNP. CONCLUSION: Radiation-induced CRS patients exhibited greater squamous metaplasia and subepithelial edema when compared with a cohort of patients with CRSsNP, and decreased eosinophilia and basement membrane thickening compared with a cohort of CRSwNP patients. CRSr cases demonstrated no difference in eosinophilia or neutrophilia compared with CRSsNP, and decreased eosinophilia compared with CRSwNP, lending further credence to the unique nature of radiation in the development of CRS in this patient group. These findings may have major implications with regard to extent of surgical intervention and medical management.

Association of Insurance and Community-Level Socioeconomic Status With Treatment and Outcome of Squamous Cell Carcinoma of the Pharynx.

Importance: Community-level socioeconomic status, particularly insurance status, is increasingly becoming important as a possible determinant in patient outcomes. Objective: To determine the association of insurance and community-level socioeconomic status with outcome for patients with pharyngeal squamous cell carcinoma (SCC). Design, Setting, and Participants: This study extracted data from more than 1500 Commission on Cancer-accredited facilities collected in the National Cancer Database. A total of 35 559 patients diagnosed with SCC of the pharynx from 2004 through 2013 were identified. The χ2 test, Kaplan-Meier method, and Cox regression models were used to analyze data from April 1, 2016, through April 16, 2017. Main Outcomes and Measures: Overall survival was defined as time to death from the date of diagnosis. Results: Among the 35 559 patients identified (75.6% men and 24.4% women; median age, 61 years [range, 18-90 years]), 15 146 (42.6%) had Medicare coverage; 13 061 (36.7%), private insurance; 4881 (13.7%), Medicaid coverage; and 2471 (6.9%), no insurance. Uninsured patients and Medicaid recipients were more likely to be younger, black, or Hispanic; to have lower median household income and lower educational attainment; to present with higher TNM stages of disease; and to start primary treatment at a later time from diagnosis. Those with private insurance (reference group) had significantly better overall survival than uninsured patients (hazard ratio [HR], 1.72; 95% CI, 1.59-1.87), Medicaid recipients (HR, 1.99; 95% CI, 1.88-2.12), or Medicare recipients (HR, 2.07; 95% CI, 1.99-2.16), as did those with median household income of at least $63 000 (reference) vs $48 000 to $62 999 (HR, 1.19; 95% CI, 1.13-1.26), $38 000 to $47 999 (HR, 1.31; 95% CI, 1.24-1.38), and less than $38 000 (HR, 1.51; 95% CI, 1.43-1.59). On multivariable analysis, insurance status and median household income remained independent prognostic factors for overall survival even after accounting for educational attainment, race, Charlson/Deyo comorbidity score, disease site, and TNM stage of disease. Conclusions and Relevance: Insurance status and household income level are associated with outcome in patients with SCC of the pharynx. Those without insurance and with lower household income may significantly benefit from improving access to adequate, timely medical care. Additional investigations are necessary to develop targeted interventions to optimize access to standard medical treatments, adherence to physician management recommendations, and subsequently, prognosis in these patients at risk.

Racial disparities in anaplastic oligodendroglioma: An analysis on 1643 patients.

The objective of our study is to determine the influence of race on overall survival (OS) for anaplastic oligodendroglioma (AO). Data were extracted from the National Cancer Data Base (NCDB). Chi-square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 1643 patients with AO were identified. 1386 (84.3%) were White, 83 (5.0%) Black, 133 (8.1%) Hispanic, and 41 (2.5%) were Asian. White and Black patients were significantly older than Hispanic and Asian patients (49.3% vs. 49.4% vs. 33.1% vs. 39.0%, p=0.003). Black patients were significantly less likely to be insured than White patients (12.8 vs. 7.2%, p<0.001) and significantly more likely to have lower income than other races (p<0.001). A trend towards higher comorbidity burden and lower rate of gross total resection was seen in Black patients. Black patients had significantly worse five-year OS compared to White, Hispanic, and Asian patients (40.3% vs. 52.3% vs. 67.8% vs. 67.7%, p=0.028). Of those who received adjuvant chemoRT, Black patients still had significantly worse OS compared to White patients (p=0.021). On multivariate analysis, Black race, older age at diagnosis, and not receiving adjuvant chemoradiotherapy were independent prognostic factors for worse OS in anaplastic oligodendroglioma. Future studies are warranted to help determine predictors for unfavorable molecular status, ways to optimize management of comorbidities, and interventions to help ensure adequate access to medical care for all patients to better care for those who may be at more risk for poorer outcome.

Influence of insurance status and income in anaplastic astrocytoma: an analysis of 4325 patients.

To determine the impact of insurance status and income for anaplastic astrocytoma (AA). Data were extracted from the National Cancer Data Base. Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 4325 patients with AA diagnosed from 2004 to 2013 were identified. 2781 (64.3%) had private insurance, 925 (21.4%) Medicare, 396 (9.2%) Medicaid, and 223 (5.2%) were uninsured. Those uninsured were more likely to be Black or Hispanic versus White or Asian (p < 0.001), have lower median income (p < 0.001), less educated (p < 0.001), and not receive adjuvant chemoradiation (p < 0.001). 1651 (38.2%) had income ≥$63,000, 1204 (27.8%) $48,000-$62,999, 889 (20.5%) $38,000-$47,999, and 581 (13.4%) had income <$38,000. Those with lower income were more likely to be Black or Hispanic versus White or Asian (p < 0.001), uninsured (p < 0.001), reside in a rural area (p < 0.001), less educated (p < 0.001), and not receive adjuvant chemoradiation (p < 0.001). Those with private insurance had significantly higher overall survival (OS) than those uninsured, on Medicaid, or on Medicare (p < 0.001). Those with income ≥$63,000 had significantly higher OS than those with lower income (p < 0.001). On multivariate analysis, age, insurance status, income, and adjuvant therapy were independent prognostic factors for OS. Being uninsured and having income <$38,000 were independent prognostic factors for worse OS in AA. Further investigations are warranted to help determine ways to ensure adequate medical care for those who may be socially disadvantaged so that outcome can be maximized for all patients regardless of socioeconomic status.

Anaplastic astrocytoma: prognostic factors and survival in 4807 patients with emphasis on receipt and impact of adjuvant therapy.

To determine the receipt and impact of adjuvant therapy on overall survival (OS) for anaplastic astrocytoma (AA). Data were extracted from the National Cancer Data Base (NCDB). Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 4807 patients with AA diagnosed from 2004 to 2013 who underwent surgery were identified. 3243 (67.5 %) received adjuvant chemoRT, 525 (10.9 %) adjuvant radiotherapy (RT) alone, 176 (3.7 %) adjuvant chemotherapy alone and 863 (18.0 %) received no adjuvant therapy. Patients were more likely to receive adjuvant chemoRT if they were diagnosed in 2009-2013 (p = 0.022), were ≤ 50 years (p < 0.001), were male (p = 0.043), were Asian or White race (p < 0.001), had private insurance (p < 0.001), had income ≥$38,000 (p < 0.001), or underwent total resection (p < 0.003). Those who received adjuvant chemoRT had significantly better 5-year OS than the other adjuvant treatment types (41.8 % vs. 31.2 % vs. 29.8 % vs. 27.4 %, p < 0.001). This significant 5-year OS benefit was also observed regardless of age at diagnosis. Of those undergoing adjuvant chemoRT, those receiving ≥59.4 Gy had significantly better 5-year OS than those receiving <59.4 Gy (44.4 % vs. 25.9 %, p < 0.001). There was no significant difference in OS when comparing 59.4 Gy to higher RT doses. On multivariate analysis, receipt of adjuvant chemoRT, age at diagnosis, extent of disease, and insurance status were independent prognostic factors for OS. Adjuvant chemoRT is an independent prognostic factor for improved OS in AA and concomitant chemoRT should be considered for all clinically suitable patients who have undergone surgery for the disease.

Utilization and impact of adjuvant therapy in anaplastic oligodendroglioma: an analysis on 1692 patients.

The aim of this study was to determine the utilization rates and impact of adjuvant therapy on overall survival (OS) for anaplastic oligodendroglioma (AO). Data were extracted from the National Cancer Data Base (NCDB). Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 1692 patients with AO who underwent surgery were identified. 945 (55.9 %) received adjuvant radiotherapy with concomitant chemotherapy (chemoRT), 102 (6.0 %) adjuvant radiotherapy (RT) sequentially followed by chemotherapy, 244 (14.4 %) adjuvant RT alone, and 401 (23.7 %) received no adjuvant therapy. Patients were more likely to receive adjuvant chemoRT if they were diagnosed in 2009-2013 vs. 2004-2008 (p < 0.001), had Karnofsky Performance Status >70 vs. <70 (p = 0.018), had private insurance vs. Medicaid vs. no insurance (p < 0.001), or had median income ≥$63,000 vs. <$63,000 (p = 0.014). Those who received adjuvant chemoRT (concomitant or sequential) had significantly better 5-year OS than those who received adjuvant RT alone or no adjuvant therapy (59.8 % vs. 65.0 % vs. 44.9 % vs. 45.6 %, p < 0.001). This significant 5-year OS benefit was also observed regardless of age. There was no difference in OS when comparing concomitant chemoRT to sequential RT and chemotherapy (p = 0.481). On multivariate analysis, receipt of adjuvant chemoRT (concomitant or sequential) remained an independent prognostic factor for improved OS. Adjuvant chemoRT (concomitant or sequential) is an independent prognostic factor for improved OS in anaplastic oligodendroglioma and should be considered for all clinically suitable patients who have undergone surgery for the disease.

Establishing a targeted plan for prophylactic dental extractions in patients with laryngeal cancer receiving adjuvant radiotherapy.

OBJECTIVE: The purpose of this study was to determine dose delivered to individual mandibular tooth-bearing regions during adjuvant intensity-modulated radiotherapy for laryngeal cancers. STUDY DESIGN: Twenty patients with laryngeal cancer treated with intensity-modulated radiotherapy were included. Individual mandibular tooth-borne areas were manually contoured. Average doses were calculated for individual teeth. RESULTS: Doses to individual teeth increased with more posterior location. Highest dose was observed for third molar (M3) (43.1 Gy; P < .001). Doses to molars and premolars correlated with T- and N-stage (P = .007; P < .001, respectively). For ipsilateral nodal disease, there was no difference between the doses to ipsilateral teeth and contralateral teeth. Only in N2 c tumors, dose was above our threshold for extraction for M3 only (51.5 Gy). CONCLUSIONS: T- and N-stage drive dose to individual mandibular tooth-borne areas. With the exception of the posterior molars, particularly in node-positive patients, radiation exposure falls below the threshold reported for pre-RT tooth extractions (50 Gy). We concluded that a more conservative approach to prophylactic tooth extraction with a greater emphasis on dental management may be warranted for the prevention of osteoradionecrosis in patients with laryngeal cancer receiving adjuvant RT.

Combination Trimodality Therapy Using Vismodegib for Basal Cell Carcinoma of the Face.

Background. For large basal cell carcinomas (BCCs) of the head and neck, definitive surgery often requires extensive resection and reconstruction that may result in prolonged recovery and limited cosmesis. Vismodegib, a small-molecule inhibitor of the hedgehog pathway, is approved for advanced and metastatic BCCs. We present a case of advanced BCC treated with combination of vismodegib, radiotherapy, and local excision resulting in excellent response and cosmesis. Case Presentation. A 64-year-old gentleman presented with a 5-year history of a 7 cm enlarging right cheek mass, with extensive vascularization, central ulceration, and skin, soft tissue, and buccal mucosa involvement. Biopsy revealed BCC, nodular type. Up-front surgical option involved a large resection and reconstruction. After multidisciplinary discussion, we recommended and he opted for combined modality of vismodegib, radiotherapy, and local excision. The patient tolerated vismodegib well and his right cheek lesion decreased significantly in size. He was then treated with radiotherapy followed by local excision that revealed only focal residual BCC. Currently, he is without evidence of disease and has excellent cosmesis. Conclusions. We report a case of locally advanced BCC treated with trimodality therapy with vismodegib, radiotherapy, and local excision, resulting in excellent outcome and facial cosmesis, without requiring extensive resection or reconstructive surgery.

Successful delivery of adjuvant external beam radiotherapy for ependymoma in a patient with Ondine׳s curse.

Ondine׳s curse is a rare, potentially life-threatening disorder characterized by loss of automatic breathing during sleep and preserved voluntary breathing. It is seldom encountered in the radiotherapy clinic but can pose significant technical challenges and safety concerns in the delivery of a prescribed radiation course. We report a unique case of successful delivery of radiotherapy for ependymoma in a patient with Ondine׳s curse. A 53-year-old gentleman presented with vertigo when lying down. Brain magnetic resonance imaging revealed an enhancing mass in the floor of the fourth ventricle. He underwent maximal safe resection. Pathology revealed ependymoma. The patient was referred for radiotherapy. Computed tomography simulation was performed in supine position with 3-point thermoplastic mask immobilization. Sequential TomoTherapy plans were developed. At first scheduled treatment, shortly after mask placement, his arms went limp and he was unresponsive. Vitals showed oxygen saturation 83%, pulse 127, and blood pressure 172/97mmHg. He was diagnosed with Ondine׳s curse thought secondary to previous brainstem damage; the combination of lying flat and pressure from the mask was causing him to go into respiratory arrest. As supine positioning did not seem clinically advisable, he was simulated in prone position. A RapidArc plan and a back-up conformal plan were developed. Prescriptions were modified to meet conservative organs-at-risk constraints. Several strategies were used to minimize uncertainties in set-up reproducibility associated with prone positioning. He tolerated prone RapidArc treatments well. The report highlights the importance of applying practical patient safety and treatment planning/delivery strategies in the management of this challenging case.

Radiation-associated toxicities in the treatment of high-grade gliomas.

This article gives a brief historical overview of the development of standard management for high-grade gliomas (HGGs). The current standard of care, trimodality therapy with maximal safe resection followed by involved-field radiotherapy (RT) with concomitant/adjuvant temozolomide, confers median survival of 14.6 months, and a modest but measurable proportion (9.8%) of patients survives 5 or more years. We review the toxicities associated with irradiation of the central nervous system for patients with HGG, with focus on the pathophysiology, clinical manifestations, and potential preventative strategies for long-term neurocognitive dysfunction, which remains a pervasive, progressive, and clinically devastating sequela of trimodality therapy. Treatment of cognitive decline after RT is limited, and strategies for preventing this complication are being investigated.

Stereotactic radiosurgery boost to the resection cavity for cerebral metastases: Report of overall survival, complications, and corticosteroid protocol.

BACKGROUND: This report focuses on the overall survival and complications associated with treatment of cerebral metastases with surgical resection followed by stereotactic radiosurgery (SRS). Management and complications of corticosteroid therapy are underreported in the literature but represent an important source of morbidity for patients. METHODS: Fifty-nine consecutive patients underwent surgical resection of a cerebral metastasis followed by SRS to the cavity. Patient charts were reviewed retrospectively to ascertain overall survival, local control, surgical complications, SRS complications, and corticosteroid complications. RESULTS: Our mean follow-up was 14.4 months (median 12.0 months, range 0.9-62.9 months). Median overall survival in this series was 15.25 months and local control was 98.3%. There was a statistically significant survival benefit conferred by Radiation Therapy Oncology Group recursive partitioning analysis Classes 1 and 2. The surgical complication rate was 6.8% while the SRS complication rate was 2.4%. Corticosteroid complications are reported and dependence at 1 month was 20.3%, at 3 months 6.8%, at 6 months 1.7%, and at 12 months no patients remained on corticosteroid therapy. CONCLUSIONS: Overall survival and local control with this treatment paradigm compare well to the other published literature. Complications associated with this patient population are low. A corticosteroid tapering protocol is proposed and demonstrated lower rates of steroid-related complications and dependence than previously reported.

Integral dose delivered to normal brain with conventional intensity-modulated radiotherapy (IMRT) and helical tomotherapy IMRT during partial brain radiotherapy for high-grade gliomas with and without selective sparing of the hippocampus, limbic circuit and neural stem cell compartment.

INTRODUCTION: We compared integral dose with uninvolved brain (IDbrain ) during partial brain radiotherapy (PBRT) for high-grade glioma patients using helical tomotherapy (HT) and seven field traditional inverse-planned intensity-modulated radiotherapy (IMRT) with and without selective sparing (SPA) of contralateral hippocampus, neural stem cell compartment (NSC) and limbic circuit. METHODS: We prepared four PBRT treatment plans for four patients with high-grade gliomas (60 Gy in 30 fractions delivered to planning treatment volume (PTV60Gy)). For all plans, a structure denoted 'uninvolved brain' was created, which included all brain tissue not part of PTV or standard (STD) organs at risk (OAR). No dosimetric constraints were included for uninvolved brain. Selective SPA plans were prepared with IMRT and HT; contralateral hippocampus, NSC and limbic circuit were contoured; and dosimetric constraints were entered for these structures without compromising dose to PTV or STD OAR. We compared V100 and D95 for PTV46Gy and PTV60Gy, and IDbrain for all plans. RESULTS: There were no significant differences in V100 and D95 for PTV46Gy and PTV60Gy. IDbrain was lower in traditional IMRT versus HT plans for STD and SPA plans (mean IDbrain 23.64 Gy vs. 28 Gy and 18.7 Gy vs. 24.5 Gy, respectively) and in SPA versus STD plans both with IMRT and HT (18.7 Gy vs. 23.64 Gy and 24.5 Gy vs. 28 Gy, respectively). CONCLUSIONS: In the setting of PBRT for high-grade gliomas, IMRT reduces IDbrain compared with HT with or without selective SPA of contralateral hippocampus, limbic circuit and NSC, and the use of selective SPA reduces IDbrain compared with STD PBRT delivered with either traditional IMRT or HT.

Current status of immunotherapy and gene therapy for high-grade gliomas.

BACKGROUND: Despite improvements in surgical technique, radiation therapy delivery, and options for systemic cytotoxic therapy, the median survival for patients with newly diagnosed glioblastoma multiforme remains poor at 15 months with trimodality therapy. Multiple immunologic approaches are being tested to enhance the response of these tumors to existing therapy and/or to stimulate innate immune responses. METHODS: We review the existing data that support the continued development of immunologic therapy in the treatment armamentarium against glioblastoma multiforme, with a focus on clinical data documenting outcomes. RESULTS: In phase I and phase II trials, antitumor vaccines (dendritic and formalin-fixed) have demonstrated clinical efficacy with mild toxicity, suggesting that innate immune responses can be amplified and directed against these tumors. Suicide gene therapy (gene-mediated cytotoxic therapy) using a number of viral vectors and molecular pathways has also shown efficacy in completed phase I and ongoing phase II trials. In addition, neural stem cells are being investigated as vectors in this approach. CONCLUSIONS: Although phase III data are needed before immunologic therapies can be widely implemented into clinical practice, the existing phase I and phase II data suggest that these therapies can produce meaningful and sometimes durable responses in patients with glioblastoma multiforme with mild toxicity compared with other existing therapies.